Sodium Bicarbonate → 4-{[6-(3-Methanesulfonyl-4-methoxy-phenyl)-4-(1-trifluoromethyl-cyclopropylamino)-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}-benzenesulfonamide

HRID 42364Notes

Reaction equation

HRID 42364 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[C:7]([NH:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([S:28]([NH2:31])(=[O:30])=[O:29])=[CH:24][CH:23]=3)[N:8]=[C:9]([NH:12][C:13]3([C:16]([F:19])([F:18])[F:17])[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.[CH3:32][S:33]([C:36]1[CH:37]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:39]=[CH:40][C:41]=1[O:42][CH3:43])(=[O:35])=[O:34].C(=O)(O)[O-].[Na+]>COCCOC>[CH3:32][S:33]([C:36]1[CH:37]=[C:38]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]=[C:7]([NH:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([S:28]([NH2:31])(=[O:30])=[O:29])=[CH:24][CH:23]=4)[N:8]=[C:9]([NH:12][C:13]4([C:16]([F:18])([F:19])[F:17])[CH2:15][CH2:14]4)[C:10]=3[N:11]=2)[CH:39]=[CH:40][C:41]=1[O:42][CH3:43])(=[O:34])=[O:35]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 592512211,3,2-Dioxaborolane, 2-[4-methoxy-3-(methylsulfonyl)phenyl]-4,4,5,5-tetramethyl-HCID 866536224-{[6-Chloro-4-(1-trifluoromethyl-cyclopropylamino)-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}benzenesulfonamide

Product 1

HCID 446216954-{[6-(3-Methanesulfonyl-4-methoxy-phenyl)-4-(1-trifluoromethyl-cyclopropylamino)-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}-benzenesulfonamideYield 40%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
65 °C

Procedure

4-{[6-Chloro-4-(1-trifluoromethyl-cyclopropylamino)-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}benzenesulfonamide (0.100 g, 0.23 mmol) was combined with 2-(3-methanesulfonyl-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.091 g, 0.34 mmol, see Scheme 7), palladium tetrakistriphenylphosphine (0.013 g, 0.011 mmol) and sodium bicarbonate (1.5 mL of a saturated aqueous solution). The mixture was suspended in DME (3 mL) and heated to 65° C. for 1 h. Crude product was precipitated by the addition of water (5 mL). The precipitate was filtered and purified by reverse phase HPLC (5-100% ACN/H2O+0.1% TFA) to give 0.056 g (40% yield) of the title compound, and was characterized by its NMR and mass spectrum as follows: 1H NMR (d6-DMSO): d 1.38-1.26 (m, 4H), 3.31 (s, 3H), 4.06 (s, 3H), 4.79 (m, 2H), 7.34 (s, 2H), 7.46 (d, J=8.7 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.78 (d, J=8.4 Hz, 2H), 8.01 (d, J=9.0 Hz, 1H), 8.45-8.41 (m, 2H), 8.90 (d, J=11.4 Hz, 1H), 9.08 (bs, 1H), 10.15 (bs, 1H): MS (m/z): 623.2 ([M+H]+, 100).

Workup

  1. customCrude product was precipitated by the addition of water (5 mL)
  2. filtrationThe precipitate was filtered
  3. custompurified by reverse phase HPLC (5-100% ACN/H2O+0.1% TFA)

Sources & evidence

ORD record
ord-13a1a4c073bf450db4d3cb4647d63adf
Source dataset
uspto-grants-2013_09
Patent number
US08536187B2

Reaction notes

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